It is with much refreshed energy that we are welcoming you, our readers, to a new year and a new decade. Despite a seemingly somewhat rudderless world, there is reason for optimism: The economy is performing remarkably well, which significantly impacts fertility practice since, at least in the U.S., studies have demonstrated that IVF cycle numbers (in other words, fertility treatments) rise and fall in parallel to economic conditions. In good economic times the desire for having children increases and, not surprisingly, the opposite happens during poorer economic conditions. We, therefore, are looking forward to another very busy year at CHR.
This is also an opportune moment to remind patients who in the past achieved pregnancies with CHR’s help, and are considering the possibility of another pregnancy during 2020, that at least some tests will have to be repeated and ovaries will, likely, have to be prepared over a few weeks to months before another treatment cycle can be initiated. We, therefore, suggest that you contact us for an initial appointment with your physician at least 3-4 months ahead of any planned new treatment cycle.
The year 2020 in New York state, in addition, now finally offers a legislatively expanded insurance coverage mandate, which should for many New York state residents provide more and better access to fertility treatments, including IVF. There are exceptions to the mandate and it, unfortunately, does not apply to everybody, but should your insurance plan in the past have excluded coverage for IVF, you should definitely check with your benefit manager whether that has changed in the new year.
In addition, we here at CHR, are very pleased that the subject of unnecessary add-ons to IVF, suddenly, seems to be receiving more attention in the lay media and medical literature. A recent editorial in The New York Times on the subject attracted considerable attention and the last issues of Fertility & Sterility, the official organ of the American Society for Reproductive Medicine (ASRM) dedicated significant page volume to the subject (see further discussion starting on page 3 of this issue of the VOICE).
As readers of the VOICE, of course, know based on how many times we have addressed different aspects of this issue in these pages, CHR has been arguing against the increasing utilization of many of these add-ons for many years. For CHR’s investigators, who for over a decade often have been subjected to, at times rather unfair, attacks from colleagues with opposing opinions, these developments are, of course, highly rewarding. They not only reaffirm one more time that, when CHR investigators express opinions in the medical literature, they usually know what they are talking about and are proven correct. Fortunately, like in science in general, in medicine the truth, ultimately, also always wins out.
Since CHR was founded in July of 1981 (in those times in Chicago), CHR investigators on quite a number of important occasions were proven right when most colleagues thought differently: When, as early as in August of 1983, Gleicher et al reported in The Lancet the first vaginal egg retrieval under ultrasound control (at that time, egg retrievals were performed in the operating room), nobody initially wanted to believe it. Opinion, of course, quite quickly changed and vaginal egg retrieval became the routine.
When in 1988, Confino et al in the American Journal of Obstetrics and Gynecology reported the first successful tubal catheterizations (in place of major surgery) to overcome tubal obstructions, a prominent colleague penned an editorial in Fertility & Sterility claiming that such catheterizations were not anatomically possible because of the narrowness of the intramural portion of the fallopian tube. CHR investigators were, of course, correct in that instance as well, and tubal catheterizations saved in those years many women from major abdominal surgeries until pregnancy rates with IVF improved to such a degree that tubal catheterizations became a rarity. CHR, indeed, performed hundreds, if not thousands, of these procedures on an ambulatory basis, with catheters fed into the fallopian tubes transvaginally under X-ray control, like in a cardiac or vascular catheterization. To this day, radiologists perform these procedures routinely.
When, in 2005, Drs. Barad and Gleicher published their first report on androgen supplementation in selected infertile women with dehydroepiandrosterone (DHEA) in Fertility & Sterility, it was only the first of 29 peer-reviewed publications from CHR addressing this subject in the literature up to this point. The whole field of infertility, at that point, however, considered giving androgens (male hormones) to infertile women a rather “crazy” idea because androgens were widely considered “toxic” for ovaries.
CONFLICT STATEMENT: Please note that CHR and both physicians are co-inventors on a number of U.S. patents, claiming therapeutic benefits from androgen supplementation, including DHEA, in infertile women with low androgen levels. Both physicians and CHR also receive royalties for these patents from a number of companies that produce and sell DHEA for infertility indications. Dr. Gleicher is also a shareholder in Fertility Nutraceuticals, LLC, a producer of DHEA. Please consider these facts when reading here about supplementation with DHEA and other androgens.
Though the subject has remained somewhat controversial because of absence of properly conducted clinical trials, as of 2019, it has been estimated that up to two-thirds of IVF centers worldwide supplement some of their patients with androgens, often with DHEA. At CHR, such supplementation has been routine since 2005. Without such supplementation, CHR would not have been able to achieve its worldwide reputation of being the leading IVF center in the world when it comes to IVF treatments of “older” ovaries. In this context, CHR reported in 2018 the so-far two oldest women who conceived through IVF with use of their own eggs. They were both just days removed from age 48 when having their embryos transferred in a fresh IVF cycle, without any add-ons besides androgen supplementation and human growth hormone (HGH). (For a brief update on the utilization of HGH in infertile women, see article on page 14.)
The term “add-ons” was first used by British colleagues, referring to additions to what, roughly up to 2010, were universally viewed as standard ways to perform IVF. Since IVF became a clinical procedure routinely offered to infertile patients in the early 1980s, live birth rates, more or less constantly, improved all over the world for approximately 30 years. This trend started changing around 2009-2010, with live birth rates initially plateauing and then staring to decline, with declines becoming precipitous over the last 3-4 years of published data. (See also the article on page 3 on our views on add-ons.)
The conclusion that, starting around 2009-2010, something “bad” happened in worldwide IVF, is, therefore, inescapable. In the opinion of CHR’s investigators, what caused these reversals in IVF outcome trends was obvious: In often well-meant changes to how IVF had been practiced up to that point, some IVF centers started propagating practice changes with at times inflated claims. Moreover, in attempts to offer “something new” at all costs, some of these claims, unfortunately, were outright false. In latter circumstances, the newly applied treatments not only failed to deliver promised improvements in IVF outcomes but, actually, at least in selected patient populations, significantly reduced pregnancy and live birth chances.
Curiously, many of these “fake news” articles were actually published in prestigious medical journals, thereby giving these fake claims additional credibility. How that happened remains to be determined, but it was not only poorly conducted peer review. At times, economic conflicts of interest, of reviewers, commentators and editors, were only too obvious.
Add-ons to IVF practice, consequently, since ca. 2010 have become the most strenuous disagreements between CHR investigators and many colleagues. Below are the add-ons CHR has been the most concerned about:
PGT-A was, likely, the most consequential add-on because it not only adversely affects IVF outcomes in isolation (as all the other add-ons do) but, in addition, also adversely affects IVF outcomes indirectly because PGT-A requires routine extended embryo culture to blastocyst stage (often associated with eSET) as well as embryo banking. Consequently, rapidly increasing utilization of PGT-A around the world, indirectly, affected general IVF practice to significant degrees by increasing utilization of extended embryo culture, eSET and embryo cryopreservation (“embryo banking”).
As economic interests from add-ons, and especially from PGT-A, assumed increasing importance for IVF centers and a rapidly growing support industry around PGT-A, the conflict between proponents and opponents (CHR included) accelerated. A formal analysis of this conflict is, indeed, in press and should be published in early 2020. Among a number of other themes, this issue of the VOICE addresses CHR’s longstanding concerns about above noted add-ons.
In this month's CHR VOICE, we cover:
Read the January 2020 CHR _VOICE _in PDF.
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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